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Numerous studies have shown their beneficial effects in prevention of cardiovascular disease through cholesterol\u2010lowering and anti\u2010atherosclerotic properties. Although some statin patients may experience muscle\u2010related symptoms, severe side effects of statin therapy are rare, primarily due to extensive first\u2010pass metabolism in the liver. Skeletal muscles appear to be the main site of side effects; however, recently some statin\u2010related adverse effects have been described in tendon. The mechanism behind these side effects remains unknown. This is the first study that explores tendon\u2010specific effects of statins in human primary tenocytes. The cells were cultured with different concentrations of lovastatin for up to 1 week. No changes in cell viability or morphology were observed in tenocytes incubated with therapeutic doses. Short\u2010term exposure to lovastatin concentrations outside the therapeutic range had no effect on tenocyte viability; however, cell migration was reduced. Simvastatin and atorvastatin, two other drug family members, also reduced the migratory properties of the cells. Prolonged exposure to high concentrations of lovastatin induced changes in cytoskeleton leading to cell rounding and decreased levels of mRNA for matrix proteins, but increased BMP\u20102 expression. Gap junctional communication was impaired but due to cell shape change and separation rather than direct gap junction inhibition. These effects were accompanied by inhibition of prenylation of Rap1a small GTPase. Collectively, we showed that statins in a dose\u2010dependent manner decrease migration of human tendon cells, alter their expression profile and impair the functional network, but do not inhibit gap junction function. J. Cell. Physiol. 230: 2543\u20132551, 2015. \u00a9 2015 The Authors. <jats:italic>Journal of Cellular Physiology<\/jats:italic> Published by Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25010","type":"journal-article","created":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T22:04:03Z","timestamp":1428012243000},"page":"2543-2551","source":"Crossref","is-referenced-by-count":15,"title":["Lovastatin\u2010Mediated Changes in Human Tendon Cells"],"prefix":"10.1002","volume":"230","author":[{"given":"Maria","family":"Kuzma\u2010Kuzniarska","sequence":"first","affiliation":[{"name":"Botnar Research Centre Institute of Musculoskeletal Sciences Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences University of Oxford Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah R.","family":"Cornell","sequence":"additional","affiliation":[{"name":"Botnar Research Centre Institute of Musculoskeletal Sciences Nuffield 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